The ultimate goal of the proposed research is to fully understand the normal and abnormal contraction of cardiac chambers as the hydraulic energy sources working in the hydraulic loop of circulation. To this end, we propose to analyze interactions between left and right ventricles as well as their interactions with the arterial and venous hydraulic impedance properties. The pump function will be evaluated by endsystolic pressure-volume relationship (ESPVR) measured in vivo or in vitro. The research will proceed from physiological heart preparations to models of cardiovascular diseases so that the resultant information will eventually contribute to cardiological diagnostics and therapeutics. Specific Aim I is to systemically determine how ESPVR of left or right ventricle changes with time (transient response analyses) after a step change in preload and afterload in excised canine heart. Specific Aim II is to test a hypothesis that the ESPVR of a regularly beating ventricule under a given contractility can be accurately estimated by perturbing the ventricle with extrasystolic and postextrasystolic potentiated (PESP) beats. Specific Aim III is to quantify in excised hearts the trans-septal interventricular crosstalk in terms of pressure and volume crosstalk gain from either ventricle to the other. Displacement of the septum will also be measured and correlated with the transeptal pressure and its history. Specific Aim IV is direct and simultaneous determination of the ESPVRs of human left and right ventricles in excised abnormal hearts from recipients of heart transplantation. Specific Aim V is validation of ESPVR as an index of ventricular contractility in in vivo canine ventricles using radiopaque marker biplane cine-measurement of volumes. Specific Aim VI is analyses in excised canine heart of the effect of dynamic factors such as arterial reflection waves and retrograde venous impedance characteristics on the left and right ventricular stroke volumes, utilizing computer stimulation of arterial and venous loads.